Search Results (286)

Background and Objectives: This study aimed to evaluate the treatment outcomes of adults with pulmonary drug-susceptible tuberculosis (DS-TB) in Lithuania over 22 years, and to examine associations between treatment outcomes, various risk factors, and temporal trends. Materials and Methods: A retrospective cohort analysis was conducted using data from the National Tuberculosis Information System from 2000 to 2021. A total of 18,697 adult patients with DS-TB were included. Patients were grouped into three time periods: Period I (2000–2007), Period II (2008–2015), and Period III (2016–2021). Treatment outcomes were categorized as successful (treatment completed with recovery) or unsuccessful (patients who encountered treatment failure, died during treatment, or converted to drug-resistant tuberculosis). Associations with individual risk factors, including smoking, alcohol use, comorbidities, and sociodemographic variables, were analyzed. Results: Treatment success rates improved steadily across the study periods: 82.3% in Period I, 84.4% in Period II, and 87.6% in Period III. Mortality rates declined over time but remained substantial: 17.1%, 15.2%, and 12.0% in Periods I, II, and III, respectively. Non-lethal treatment failures decreased slightly (0.6%, 0.4%, and 0.4%). Multivariate analysis identified significant associations between treatment failure and multiple risk factors, including low BMI, male gender, unemployment, homelessness, smoking, alcohol and substance use, and comorbid conditions such as cancer, cardiovascular disease, chronic lung disease, diabetes mellitus, HIV, and renal failure. Conclusions: Treatment outcomes for DS-TB in Lithuania have improved over the past two decades; however, certain modifiable risk factors—such as low BMI, homelessness, substance use, and comorbidities—remain strongly linked to treatment failure. To further improve outcomes, targeted interventions such as nutritional support, housing programs, and integrated addiction services should be prioritized for high-risk groups within national TB control efforts. Full article

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis and is associated with high morbidity and mortality, especially in resource-limited settings. In Mozambique, where both tuberculosis and HIV are highly prevalent, TBM poses significant diagnostic and therapeutic challenges. This study aimed to describe the clinical characteristics and to identify predictors of TBM mortality among persons living with HIV (PLWH) in a rural hospital in Mozambique. Methods: We conducted a retrospective cohort study at Carmelo Hospital of Chokwe (CHC) between 2015 and 2020. We included 372 PLWH diagnosed with TBM (PTBM); data on demographics, clinical presentation, and laboratory findings were extracted from patient records. TBM diagnosis was considered for confirmed cases based on a hospital-adapted algorithm incorporating clinical features, cerebrospinal fluid (CSF) analysis, TB-LAM, and Xpert MTB/RIF testing. Cox proportional hazard models were used to identify independent predictors of mortality, and Kaplan–Meier survival curves with log-rank tests were used to assess survival differences across clinical subgroups. Significance was considered at a p value ≤ 0.05 with an adjusted hazard ratio (AHR) 95% CI in the multivariate analysis. Results: Overall, 372 PTBM contributed to a total of 3720 person-months (PM) of treatment follow-up, corresponding to a mortality incidence of 3.76 deaths per 100 person-months. Factors independently associated with increased mortality included male sex (adjusted hazard ratio [aHR]: 1.80; 95% CI: 1.21–2.68; p = 0.004), BMI < 18.5 kg/m² (aHR: 2.84; 95% CI: 1.46–5.55; p = 0.002), Immunovirological failure to ART (aHR: 2.86; 95% CI: 1.56–5.23; p = 0.001), CSF opening pressure >40 cmH₂O (aHR: 2.67; 95% CI: 1.46–4.86; p = 0.001), and TBM severity grading III (aHR: 4.59; 95% CI: 1.79–11.76; p = 0.001). TBM involving other organs also significantly worsened survival (aHR: 2.03; 95% CI: 1.27–3.25; p = 0.003). Conclusions: TBM mortality in PLWH was driven by ART failure, high CSF pressure, and malnutrition. Male sex and severe neurology also increased risk. Urgent interventions are proposed: optimize ART, manage intracranial pressure, provide nutritional support, and use corticosteroids. An integrated care approach is essential to improving survival in resource-limited settings. Full article

Infectious diseases remain a global threat, with low- and middle-income countries disproportionately affected due to socio-economic and demographic vulnerabilities. Robust laboratory systems are critical for early detection, outbreak containment, and guiding effective interventions. This study aimed to map and evaluate Jordan’s laboratory diagnostic network for communicable diseases, identify gaps, and recommend strategies to strengthen capacity, harmonization, and alignment with international standards. A multi-method approach was employed in 2023 through collaboration between the Jordan Center for Disease Control and the Health Care Accreditation Council. Data were collected via (i) a desktop review of 226 national and international documents; (ii) 20 key informant interviews with stakeholders from the public, private, military, veterinary, and academic sectors; and (iii) 23 field visits across 27 laboratories in four Jordanian governorates. Data were analyzed thematically and synthesized using the LABNET framework, which outlined ten core laboratory capacities. Findings were validated through a multi-sectoral national workshop with 90 participants. The mapping revealed the absence of a unified national laboratory strategic plan, with governance dispersed across multiple authorities and limited inter-sectoral coordination. Standard operating protocols (SOPs) existed for high-priority diseases such as T.B, HIV, influenza, and COVID-19 but were lacking or outdated for other notifiable diseases, particularly zoonoses. Quality management was inconsistent, with limited participation in external quality assurance programs and minimal accreditation uptake. Biosafety and biosecurity frameworks were fragmented and insufficiently enforced, while workforce shortages, high turnover, and limited specialized training constrained laboratory performance. Despite these challenges, Jordan demonstrated strengths including skilled laboratory staff, established reference centers, and international collaborations, which provide a platform for improvement. Jordan’s laboratory network has foundational strengths but faces systemic challenges in policy coherence, standardization, quality assurance, and workforce capacity. Addressing these gaps requires the development of a national laboratory strategic plan, strengthened legal and regulatory frameworks, enhanced quality management and accreditation, and integrated One Health coordination across human, animal, and environmental health sectors. These measures will improve diagnostic reliability, preparedness, and alignment with the global health security agenda. Full article

Background: Tuberculosis (TB) remains a leading cause of death among people living with HIV (PLWH), yet diagnostic methods vary in accuracy, accessibility, and implementation. Understanding how diagnostic modality influences TB detection is essential to optimizing co-infection management. Methods: We conducted a retrospective analysis of institutional data from Bamrasnaradura Infectious Diseases Institute (BIDI), Thailand, covering 2016–2023. TB detection rates were assessed across five diagnostic methods—chest radiography (CXR), smear microscopy, acid-fast bacilli (AFB) staining, culture, and GeneXpert MTB/RIF—relative to annual HIV-related visit volumes. Results: Among 56,599 HIV-related visits, TB detection rates varied substantially by diagnostic method. CXR was the most commonly used tool, detecting TB in up to 99 cases out of 6964 visits (1.42%) in 2016, though declining to 23 cases out of 6947 visits (0.33%) in 2023. GeneXpert was employed more consistently, yielding between 7 cases out of 7577 visits (0.09%) and 13 cases out of 6593 visits (0.20%) annually. Smear microscopy and AFB staining declined markedly, falling below 0.22% after 2020. These patterns reflect a gradual transition toward molecular diagnostics, which offer improved accuracy but remain underutilized in lower-tier settings. To address these gaps, we incorporated trend analyses confirming significant temporal shifts and propose a tiered TB screening framework tailored to resource availability across healthcare levels. Conclusions: TB detection among PLWH is strongly influenced by the diagnostic method used. Unlike HIV diagnosis—which is definitive and standardized—TB diagnosis remains fragmented and resource-dependent. Context-sensitive screening protocols are urgently needed to improve TB case detection and management, particularly in lower-level HIV care facilities. Full article

Background: In 2023, tuberculosis (TB) caused 1.25 million deaths globally, remaining a leading infectious killer. Central Asia and Southern Caucasus face high TB burdens, particularly Mongolia. This review synthesizes TB prevalence data and diagnostic capabilities in these regions to support public health strategies. Methods: This systematic review aimed to synthesize current data on TB prevalence in Central Asia, Southern Caucasus, and Mongolia to support public health strategies and research priorities. A comprehensive search of PubMed and Google Scholar was conducted for English-language articles published up to 2023. Studies were assessed using a modified Newcastle–Ottawa Scale. Nine studies met the inclusion criteria, covering Kazakhstan, Kyrgyzstan, Uzbekistan, Tajikistan, Turkmenistan, Mongolia, Georgia, Armenia, and Azerbaijan. Results: TB incidence ranged from 67 per 100,000 in Kazakhstan to 190 per 100,000 in Kyrgyzstan, with the highest prevalence of 68.5% in Mongolia. TB affected men more frequently (65.3%), and the key risk factors included HIV (30.5%), comorbidities, and undernutrition. Diagnostic performance varied significantly (microscopy sensitivity, 45–65%; GeneXpert MTB/RIF, 89–96% sensitivity and 98% specificity for rifampicin resistance). Diagnostic turnaround times ranged from hours (molecular) to weeks (conventional). Only 58% of TB facilities had GeneXpert technology, with urban–rural disparities in diagnostic access. Drug-resistant TB imposed a significant economic burden, with treatment costs ranging from USD 106 to USD 3125. Conclusions: Strengthening surveillance, improving data collection, and conducting longitudinal studies are essential for designing effective TB control strategies in these regions. Significant diagnostic gaps persist across these regions, especially with regard to drug-resistant strains. Point-of-care molecular diagnostics, improved algorithms, and expanded laboratory training show promise. Future research should focus on rapid biomarker-based diagnostics, field-deployable technologies for settings with limited resources, and AI integration to enhance diagnostic accuracy and efficiency. Full article

Neglected tropical diseases (NTDs) constitute a group of infectious diseases that severely affect the health of impoverished populations, and the health, economies, and health systems of affected countries. Leishmaniasis and human African trypanosomiasis (HAT) are particularly notable, and malaria, despite not being neglected, is part of the “big three” (HIV, tuberculosis, and malaria) with high incidence, increasing the probability of infection by NTDs. Therefore, efforts are ongoing in the search for new drugs targeting the enzyme N-myristoyltransferase (NMT), a potential drug target that has been explored. Thus, we provide a review here that highlights the epidemiological data for these diseases and the importance of discovering new drugs against these agents. Here, the importance of NMT and its inhibitors is clear, with this study highlighting thiochromene, pyrazole, thienopyridine, oxadiazole, benzothiophene, and quinoline scaffolds, identified by computational methods followed by biological assays to validate the findings; for example, this study shows the action of the aminoacylpyrrolidine derivative 13 against Leishmania donovani NMT (IC₅₀ of 1.6 nM) and the pyrazole analog 23 against Plasmodium vivax NMT (IC₅₀ of 9.48 nM), providing several insights that can be used in drug design in further work. Furthermore, the selectivity and improvement in activity are related to interactions with the residues Val⁸¹, Phe⁹⁰, Tyr²¹⁷, Tyr³²⁶, Tyr³⁴⁵, and Met⁴²⁰ for leishmaniasis (LmNMT); Tyr²¹¹, Leu⁴¹⁰, and Ser³¹⁹ for malaria (PvNMT); and Lys²⁵ and Lys³⁸⁹ for HAT (TbNMT). We hope our work provides valuable insights that research groups worldwide can use to search for innovative drugs to combat these diseases. Full article

Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis complex (MTBC), which can be exacerbated by fungal infections. This study evaluated the clinical characteristics and virulence of Candida spp. in patients with tuberculosis. Antifungal sensitivity, phospholipase and proteinase production, biofilm formation, phagocytic index, and reactive oxygen (ROS) and nitrogen (RNS) species were assessed. Candida spp. were isolated from 14 patients, 28.5% women and 71.4% men, mainly from sputum and tracheal secretions. Five (35.7%) patients were co-infected with Mycobacterium, Candida, and HIV. Candida albicans (78.6%) and Candida tropicalis (21.4%) were identified in all 14 patients. All isolates showed sensitivity to amphotericin B and dose-dependent responses to fluconazole (16 μg/mL). Phospholipase activity was detected in 35.7% of the isolates, whereas all isolates showed proteinase activity (100%). A significant difference in phospholipase activity, phagocytosis, and production of reactive oxygen species (ROS) and nitrogen species (RNS) was observed when Candida isolates from patients with TB, living with or without HIV, were compared to Candida isolates from healthy individuals. All isolates were biofilm producers. This study highlights the relevance of mycoses diagnosis in patients with TB, since Candida spp. may be more virulent and contribute to the deterioration of the clinical condition. Full article

Tuberculosis (TB) remains a formidable global public health challenge. The rising prevalence of drug-resistant TB and increased human immunodeficiency virus(HIV) co-infection further exacerbate TB control efforts. Mycobacterium tuberculosis (Mtb) achieves highly heterogeneous infection outcomes (active disease, latency, or clearance) through immune evasion and host metabolic reprogramming. While conventional diagnostic techniques offer cost-effectiveness and accessibility without complex infrastructure, they are constrained by low sensitivity, prolonged turnaround times, and an inability to distinguish latent TB infection (LTBI) from active TB disease (ATB). Recent research into host-derived biomarkers provides a promising strategy to overcome diagnostic bottlenecks by deciphering characteristic molecular changes in host–pathogen interactions. This review systematically reviews advances in host-derived biomarkers for TB diagnosis, critically discussing the clinical potential, translational challenges, and future research directions of integrated multi-omics biomarker panels to enhance diagnostic sensitivity and specificity, differentiate ATB from LTBI, and guide precision therapy. Full article

Background/Objectives: Drug-resistant tuberculosis (DR-TB) presents significant challenges to public health, particularly in rural South Africa, where limited infrastructure, high HIV co-infection rates, and weak clinical governance contribute to poor treatment outcomes. This study evaluates treatment trajectories and the impact of clinical governance and public health interventions on DR-TB outcomes in the rural Eastern Cape. Methods: A retrospective cohort study was conducted among 323 laboratory-confirmed DR-TB patients treated between 2018 and 2021. Kaplan–Meier curves and Cox proportional hazards analysis identified predictors of unfavorable outcomes. Logistic regression analysis simulated the impact of enhanced clinical governance scenarios on treatment success. Results: Treatment outcomes included cure (36.2%), completion (26.0%), loss to follow up (LTFU) (9.0%), death (9.3%), failure (2.2%), and transfer (9.3%). The median treatment duration was 10 months (IQR: 9–11). Survival analysis indicates the highest risk of death and LTFU occurred in the first 6–8 months of treatment. Multivariate Cox regression revealed that primary (HR = 0.39; 95% CI: 0.23–0.68; p = 0.0017) and secondary education (HR = 0.50; 95% CI: 0.31–0.85; p = 0.0103) were significantly protective. Paradoxically, patients with pre-XDR (HR = 0.13; p = 0.034) and XDR TB (HR = 0.16; p = 0.043) showed lower hazard of poor outcomes, likely due to early mortality or referral. HIV-negative status was associated with higher risk of poor outcomes (HR = 1.74; p = 0.010). Simulations suggested that improved clinical governance via better follow-up, TB/HIV integration, and adherence support could improve treatment success by up to 20 percentage points in high-impact scenarios. Conclusions: Strengthening clinical governance through targeted interventions could substantially reduce LTFU and mortality, especially in vulnerable subgroups. A coordinated, patient-centered approach is critical for improving DR-TB outcomes in rural, high-burden settings. Full article

Background: Viral–bacterial co-infections can amplify disease severity through complex biological mechanisms. Mathematical models are critical tools for understanding these threats, but it is unclear how well they capture the underlying biology. This systematic review addresses a central question: to what extent does the current generation of models mechanistically represent co-infections, or do the mathematical assumptions underlying these models adequately represent the known biological mechanisms? Methods: Following PRISMA guidelines, we systematically reviewed the literature on mechanistic models of human virus–bacteria co-infections. A systematic search of articles on the scientific literature repositories PubMed, Scopus, and Dimensions was conducted and data on study objectives, model structure, assumptions about biological interactions (e.g., susceptibility, mortality), control measures (if evaluated), and the empirical sources used for key parameters were extracted. Results: We identified 72 studies for inclusion in this analysis. The reviewed models are consistently built on the established premise that co-infection alters disease severity and host susceptibility. However, we found they incorporate these dynamics primarily through high-level mathematical shortcuts, such as applying static “multiplicative factors” to transmission or progression rates. Our quantitative analysis also revealed questionable approaches; for example, 79% (57) of these studies relied on non-empirical sources (assumed or borrowed values) for parameter values including interaction parameters (e.g., increased susceptibility to a secondary pathogen following primary infection, or elevated mortality rates in co-infected individuals). Conclusions: An apparently unjustified practice exists in co-infection modeling, where complex biological processes are simplified to fixed numerical assumptions, often without empirical support. This practice limits the predictive reliability of current models. We identify an urgent need for data-driven parameterization and interdisciplinary collaboration to bridge the gap between biological complexity and modeling practice, thereby enhancing the public health relevance of co-infection modeling. Full article

In recent years, antiviral therapy has proved crucial in the treatment of infectious diseases, particularly infections by highly variable viruses such as human immunodeficiency virus, hepatitis B, hepatitis C, SARS-CoV-2 or bacteria such as Mycobacterium tuberculosis. Under the effect of selection pressure, this variability induces mutations that lead to resistance to antiviral and antibacterial drugs, and thus to escape from treatment. The use of Advanced Biological Laboratories (ABL) assays technology combined with next-generation sequencing (NGS) and automatized software to detect majority and minority variants involved in treatment resistance has become a mainstay for establishing therapeutic strategies. The present study demonstrated high concordance between majority and minority subtypes and mutations identified in 15 samples across four NGS platforms: ISeq100 (Illumina (San Diego, CA, USA)), MiSeq (Illumina), DNBSEQ-G400 (MGI (Santa Clara, CA, USA)) and Mk1C MinION (Oxford Nanopore (Oxford Science Park, UK)). However, nanopore technology showed a higher number of minority mutations (<20%). The analysis also validated the pooling of microbiological samples as a method for detecting mutations and genotypes in viral and bacterial organisms, using the easy-to-use DeepChek^® bioinformatics software, compatible with all four sequencing platforms. This study underlines the constant evolution of microbiological diagnostic research and the need to adapt rapidly to improve patient care. Full article

Tuberculosis (TB) remains a critical public health issue in Johannesburg, South Africa, driven by a complex interplay of individual, social, and structural factors. This study assessed the syndemic relationship between these determinants to understand their collective impact on TB burden and treatment outcomes. A cross-sectional survey was conducted among TB patients attending selected clinics, examining behavioural risks (e.g., smoking, alcohol use, HIV co-infection), social conditions (poverty, overcrowding, stigma), and structural challenges (access to healthcare, migration status). The results revealed a significant co-occurrence of TB and HIV (56.1%), alongside high rates of smoking (33.1%) and alcohol use (45.2%). Unemployment (50.2%), inadequate housing, and limited healthcare access, particularly for undocumented migrants (26.2%), were also prominent. Factor analysis demonstrated a syndemic interaction between behavioural and social determinants, underscoring the compounded vulnerability of affected populations. The findings highlight the necessity of integrating medical interventions with social and structural reforms. Recommendations include TB-HIV co-management, substance abuse programmes, improved housing, and inclusive healthcare access. A multisectoral approach addressing both health and socioeconomic inequalities is critical for comprehensive TB control in urban South African contexts. Full article

Tuberculosis remains a serious infectious disease that causes over 1.3 million deaths annually. Following the COVID-19 pandemic, the global incidence of tuberculosis has increased to 10.8 million cases. Pregnant women represent a particularly vulnerable population requiring tailored approaches to the prevention, diagnosis, and treatment of tuberculosis. SARS-CoV-2 infection may have impacted existing clinical protocols. Implementing updated methods of tuberculosis prevention, diagnosis, and treatment in pregnant women could help reduce adverse maternal and fetal outcomes. The aim of this review was to explore potential modifications in tuberculosis management among pregnant women in the post-COVID-19 era, including co-infection with SARS-CoV-2. Methods: A review was conducted, incorporating a systematic literature search across major international databases, including Medline, PubMed, Web of Science, Scopus, and Google Scholar. The search covered publications released between December 2019 and September 2024 and used targeted keywords such as “COVID-19” OR “SARS-CoV-2”, “tuberculosis” OR “TB” OR “latent tuberculosis infection” OR “pulmonary tuberculosis”, and “pregnancy” OR “pregnant women”. Results: Pregnant women living with HIV are at increased risk of developing tuberculosis, which can negatively affect both maternal and perinatal outcomes. Screening for tuberculosis is recommended for all HIV-positive pregnant women, even in the absence of clinical symptoms. Notably, immunological testing before and during pregnancy facilitates the timely and safe detection of tuberculosis infection, enabling preventive and therapeutic interventions during any stage of gestation and the early postpartum period, for the benefit of both mother and child. Drug–drug interactions play a significant role in tuberculosis management, both among anti-tuberculosis agents and with medications for comorbid conditions. Current knowledge of the pharmacokinetics and pharmacodynamics of antituberculosis agents, coupled with therapeutic drug monitoring, supports the development of individualized and effective treatment regimens, which are particularly critical for pregnant patients. Recommendations for managing tuberculosis in pregnant women after COVID-19 infection include measuring D-dimer levels, performing echocardiography, and consulting cardiologists to prevent treatment-related complications. Conclusions: Pregnant women represent a distinct subgroup of tuberculosis patients requiring individualized management. Changes observed in tuberculosis progression and treatment responses in pregnant women before and after SARS-CoV-2 infection should inform therapeutic choices, especially in cases of drug-resistant tuberculosis treated with bedaquiline. COVID-19 has been associated with increased cardiovascular risk, which may heighten the likelihood of adverse drug reactions in this population, especially given the limited therapeutic options. Further research is required to assess the long-term outcomes of latent tuberculosis infection in pregnant women and to evaluate the safety and efficacy of novel regimens for drug-resistant TB during pregnancy. Full article

Introduction: Mycobacterium tuberculosis (Mtb), the most common co-infection among people living with HIV (PLWH), aggravates the associated morbidity and mortality in these individuals; however, the immune-modulatory role of Mtb in the pathogenesis of HIV infection remains incompletely understood. Methods: We investigated the role of Mtb infection in regulating adaptive immune responses with reference to the expression of five immune checkpoint molecules (ICMs) in co-infected individuals in a cross-sectional study conducted on treatment-naïve human cohorts from North India, including PLWH, people with Mtb infection, people with HIV-Mtb co-infection, and healthy volunteers as controls. Results: The data revealed a significantly increased gene expression of TIM-3 (p = 0.0058), LAG-3 (p < 0.0001), PD-1 (p = 0.0090), and CTLA-4 (p = 0.0008). It also revealed a higher frequency of CD4⁺ and CD8⁺ T-cells surface-expressing TIM-3⁺, CTLA-4⁺, LAG-3⁺. Finally, it showed cells co-expressing two ICMs together (p < 0.05) in individuals with HIV–Mtb co-infection as compared to HIV mono-infected ones. Interestingly, the frequency of these cells correlated inversely with the absolute CD4⁺ T-cell count and positively with the plasma viral load (p < 0.05), indicating direct association with HIV disease progression. Conclusions: These findings suggest that Mtb co-infection exacerbates immune exhaustion in co-infected individuals. Targeting ICMs with pharmacological immune checkpoint inhibitors (ICIs) offers a promising approach for better clinical management of co-infected individuals. Full article

Extrapulmonary tuberculosis (EPTB) remains diagnostically challenging due to its paucibacillary nature and variable presentation. Xpert and culture are limited in EPTB diagnosis due to sampling challenges, low sensitivity, and long turnaround times. This study evaluated the performance of the MPT64 antigen detection test for diagnosing EPTB, particularly tuberculous lymphadenitis (TBLN) and tuberculous pleuritis (TBP), in a high-TB, low-HIV setting. Conducted at Gulab-Devi Hospital, Lahore, Pakistan, this study evaluated the MPT64 test’s performance against conventional diagnostic methods, including culture, histopathology, and the Xpert MTB/RIF assay. Lymph node biopsies were collected, and cell blocks were made from aspirated pleural fluid from patients clinically presumed to have EPTB. Of 338 patients, 318 (94%) were diagnosed with EPTB. For TBLN, MPT64 demonstrated higher sensitivity (84%) than Xpert (48%); for TBP, the sensitivity was 51% versus 7%, respectively. Among histopathology-confirmed TBLN cases, MPT64 outperformed both culture and Xpert (85% vs. 58% and 47%). Due to the low number of non-TB cases, specificity could not be reliably assessed. The MPT64 test shows promise as a rapid, sensitive diagnostic tool for EPTB, particularly TBLN, in routine settings. While sensitivity is notably superior to Xpert, further studies are needed to evaluate its specificity and broader diagnostic utility. Full article